PubMed Health⌕ Search

Biomedical subjects

J Gunn

Publications and source records attributed to J Gunn.

At least 19 recordsLinked to original sources
PubMed2007

Vascular delivery of c-myc antisense from cationically modified phosphorylcholine coated stents.

c-Myc is involved in the formation of neointimal hyperplasia. We investigated in vitro, ex vivo and in vivo release of antisense c-myc from cationically modified phosphorylcholine-coated stents, as well as the effects on c-Myc expression and neointima formation in a porcine coronary stent model. In vitro experiments were performed to determine optimal loading of stents with antisense. Stents loaded with labelled antisense were deployed in porcine arteries ex vivo and in vivo. Antisense was detected in the vessel wall directly surrounding the stent of pig carotid and coronary artery up to 48 h after stent deployment. Nuclear uptake was observed in endothelial and vascular smooth muscle cells. Labelled antisense within peripheral tissues in vivo was <1.0% of that within stented arterial segments. Control and antisense loaded stents implanted into 10 pig coronary arteries and analysed at 28 days post-stenting showed that lumen area within the antisense stents was significantly increased (i.e. 30.5% greater, P<0.01), whilst both neointimal area and neointimal thickness were significantly reduced (17.5% and 19.5%, respectively, P<0.01) compared to control stents. Cationically modified phosphorylcholine coated stent-based delivery of c-myc antisense is feasible with minimal systemic delivery and is associated with a reduction of in-stent neointimal hyperplasia in pig coronary arteries.

Animals↗
PubMed2006

Outcome data from the LEAP (Live, Eat and Play) trial: a randomized controlled trial of a primary care intervention for childhood overweight/mild obesity.

OBJECTIVES: To reduce gain in body mass index (BMI) in overweight/mildly obese children in the primary care setting. DESIGN: Randomized controlled trial (RCT) nested within a baseline cross-sectional BMI survey. SETTING: Twenty nine general practices, Melbourne, Australia. PARTICIPANTS: (1) BMI survey: 2112 children visiting their general practitioner (GP) April-December 2002; (2) RCT: individually randomized overweight/mildly obese (BMI z-score <3.0) children aged 5 years 0 months-9 years 11 months (82 intervention, 81 control). INTERVENTION: Four standard GP consultations over 12 weeks, targeting change in nutrition, physical activity and sedentary behaviour, supported by purpose-designed family materials. MAIN OUTCOME MEASURES: Primary: BMI at 9 and 15 months post-randomization. Secondary: Parent-reported child nutrition, physical activity and health status; child-reported health status, body satisfaction and appearance/self-worth. RESULTS: Attrition was 10%. The adjusted mean difference (intervention-control) in BMI was -0.2 kg/m(2) (95% CI: -0.6 to 0.1; P=0.25) at 9 months and -0.0 kg/m(2) (95% CI: -0.5 to 0.5; P=1.00) at 15 months. There was a relative improvement in nutrition scores in the intervention arm at both 9 and 15 months. There was weak evidence of an increase in daily physical activity in the intervention arm. Health status and body image were similar in the trial arms. CONCLUSIONS: This intervention did not result in a sustained BMI reduction, despite the improvement in parent-reported nutrition. Brief individualized solution-focused approaches may not be an effective approach to childhood overweight. Alternatively, this intervention may not have been intensive enough or the GP training may have been insufficient; however, increasing either would have significant cost and resource implications at a population level.

Body Image↗
PubMed2006

Do supervised colorectal trainees differ from consultants in terms of quality of TME surgery?

OBJECTIVE: The quality of surgical excision is held to be a major determinant of outcome following surgery for rectal cancer. Macroscopic examination of the excised mesorectum allows for reproducible assessment of the quality of surgery. We aimed to determine whether quality of excision undertaken by colorectal trainees under supervision was comparable with that performed by consultants, as measured using mesorectal grades. METHOD: A total of 130 consecutive patients undergoing potentially curative resection for primary adenocarcinoma of the rectum in our centre from 2001 to 2003 were included in the study. The pathologists graded the excised mesorectum according to staged classification proposed by Quirke. The outcome (quality of mesorectal excision and secondary outcomes including local recurrence and overall recurrence) of operations performed by consultants was compared with that of trainees. Statistical significance was tested using Pearson chi(2) test. RESULTS: Eighty-nine operations were performed by consultants and 41 by senior colorectal trainees with consultant supervision. Forty-four patients (49%) had good mesorectum when operated by consultants in comparison with 17 (41.5%) by the trainees. There was no statistically significant difference (P = 0.717) between the two groups in terms of quality of mesorectum excised after potentially curative resection. Furthermore, there were seven local recurrences in patients operated by consultants (7.8%) when compared with four in the trainee group (9.5%) and once again there was no statistical significance between the two groups (P = 0.719). CONCLUSION: We conclude that the quality of rectal cancer excision, as defined by mesorectal grades, achieved by supervised colorectal trainees is comparable with that achieved by consultants.

Aged↗
PubMed2005

Effect of the addition of a "help" question to two screening questions on specificity for diagnosis of depression in general practice: diagnostic validity study.

OBJECTIVE: To determine the validity of two written screening questions for depression with the addition of a question inquiring if help is needed. DESIGN: Cross sectional validation study. SETTING: 19 general practitioners in six clinics in New Zealand. PARTICIPANTS: 1025 consecutive patients receiving no psychotropic drugs. MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios of the two screening questions, the help question, combinations of the screening and help questions, and diagnosis by general practitioners. RESULTS: The help question alone had a sensitivity of 75% (95% confidence interval 60% to 85%) and a specificity of 94% (93% to 96%). The positive likelihood ratio for the help question was 13.0 (9.5 to 17.8) and the negative likelihood ratio was 0.27 (0.17 to 0.44). The likelihood ratio for patients wanting help today was 17.5 (11.8 to 31.9). The general practitioner diagnosis had a sensitivity of 79% (65% to 88%) and a specificity of 94% (92% to 95%). CONCLUSION: Adding a question inquiring if help is needed to the two screening questions for depression improves the specificity of a general practitioner diagnosis of depression.

Depressive Disorder↗
PubMed2005

Ultrasound-mediated delivery of TIMP-3 plasmid DNA into saphenous vein leads to increased lumen size in a porcine interposition graft model.

Progressive saphenous vein graft (SVG) narrowing and occlusion remains a major limitation of coronary artery bypass grafting and is an important target for gene therapy. Ex vivo adenoviral gene transfer of tissue inhibitor of metalloproteinase 3 (TIMP-3) reduces adverse SVG remodelling postarterialization, but concerns remain over the use of viral vectors in patients. Ultrasound exposure (USE) in the presence of echocontrast microbubbles (ECM) substantially enhances nonviral gene delivery. We investigated the effects of ultrasound-enhanced gene delivery (UEGD) of TIMP-3 plasmid on vascular remodelling in porcine SVG. Maximal luciferase activity (3000-fold versus naked plasmid alone) and TIMP-3 transgene expression in porcine vascular smooth muscle cells in vitro was achieved using USE at 1 MHz, 1.8 mechanical index (MI), 6% duty cycle (DC) in the presence of 50% (v/v) BR14 ECM (Bracco). These conditions were therefore utilized for subsequent studies in vivo. Yorkshire White pigs received carotid interposition SVG that were untransfected or had undergone ex vivo UEGD of lacZ (control) or TIMP-3 plasmids. At 28 d postgrafting, lumen and total vessel area were significantly greater in the TIMP-3 group (10.1+/-1.2 and 25.5+/-2.2 mm2, respectively) compared to untransfected (6.34+/-0.5 and 20.8+/-1.9 mm2) or lacZ-transfected (6.1+/-0.7 and 19.7+/-1.2 mm2) controls (P<0.01). These data indicate that nonviral TIMP-3 plasmid delivery by USE achieves significant biological effects in a clinically relevant model of SV grafting, and is the first study to demonstrate the potential for therapeutic UEGD to prevent SVG failure.

Animals↗
PubMed2004

Surface porous fibre-reinforced composite bulk bone substitute.

The aim of this study was to describe and evaluate the significance of a porous surface with bioactive glass granules (S53P4) covering an artificial bulk material based on polymethylmetacrylate (PMMA) and fibre-reinforced composite (FRC) technology. Effort was focused particularly on characters of the porous surface and biomechanical properties of the material in vitro , and test in vivo the implant in reconstruction in an experimental long bone segment defect model. The defect, 10 mm in length, created in the shaft of rabbit tibia, was reconstructed by the implant and fixed by intramedullary K-wires. The implant was incorporated within 4 weeks by new bone growth from the host bone covering particularly its posterior surface and cortex/implant junctions with bridging trabecular bone. Later, at 8 weeks, new bone was found also at the cortex/implant interface and in the medullary canal of the implant. Histometric measurements revealed direct bone/implant surface contact in 34% at the interface. Bioactive glass granules in the porous surface evoked the most direct contact with bone. The implants manufactured from PMMA only served as a control group, and showed significantly lower osteoconductive properties. Biomechanical measurements in vitro of fibre-reinforced PMMA specimens revealed values for bending strength and the flexural modulus to match them to human bone. This artificial bulk bone material based on PMMA/FRC technology seems to have proposing properties to be used as a bone substitute on load-bearing conditions.

Bone Substitutes↗
PubMed2004

A thermal analogy for modelling drug elution from cardiovascular stents.

Restriction of blood flow by the narrowing or occlusion of arteries is one of the most common presentations of cardiovascular disease. One treatment involves the introduction of a metal scaffold, or stent, designed to prevent recoil and to provide structural stability to the vessel. On the occasions that this treatment is ineffective, failure is usually associated with re-invasion of tissue. This can be prevented by local delivery of drugs which inhibit tissue growth. The drug might be delivered locally in a polymer coating on the stent. This paper develops and explores the use of a thermal analogue of the drug delivery process and the associated three-dimensional convection-diffusion equation to model the spatial and temporal distribution of drug concentration within the vessel wall. This allows the routine use of commercial finite element analysis software to investigate the dynamics of drug distribution, assist in the understanding of the treatment process and develop improved delivery systems. Two applications illustrate how the model might be used to investigate the effects of controllable or measurable parameters on the progression of the process. It is demonstrated that the geometric characteristics of the stent can have significant impact on the homogeneity of the dosing in the vessel wall.

Animals↗
PubMed2004

Respiratory hydrogen use by Salmonella enterica serovar Typhimurium is essential for virulence.

Based on available annotated gene sequence information, the enteric pathogen salmonella, like other enteric bacteria, contains three putative membrane-associated H2-using hydrogenase enzymes. These enzymes split molecular H2, releasing low-potential electrons that are used to reduce quinone or heme-containing components of the respiratory chain. Here we show that each of the three distinct membrane-associated hydrogenases of Salmonella enterica serovar Typhimurium is coupled to a respiratory pathway that uses oxygen as the terminal electron acceptor. Cells grown in a blood-based medium expressed four times the amount of hydrogenase (H2 oxidation) activity that cells grown on Luria Bertani medium did. Cells suspended in phosphate-buffered saline consumed 2 mol of H2 per mol of O2 used in the H2-O2 respiratory pathway, and the activity was inhibited by the respiration inhibitor cyanide. Molecular hydrogen levels averaging over 40 microM were measured in organs (i.e., livers and spleens) of live mice, and levels within the intestinal tract (the presumed origin of the gas) were four times greater than this. The half-saturation affinity of S. enterica serovar Typhimurium for H2 is only 2.1 microM, so it is expected that H2-utilizing hydrogenase enzymes are saturated with the reducing substrate in vivo. All three hydrogenase enzymes contribute to the virulence of the bacterium in a typhoid fever-mouse model, based on results from strains with mutations in each of the three hydrogenase genes. The introduced mutations are nonpolar, and growth of the mutant strains was like that of the parent strain. The combined removal of all three hydrogenases resulted in a strain that is avirulent and (in contrast to the parent strain) one that is unable to invade liver or spleen tissue. The introduction of one of the hydrogenase genes into the triple mutant strain on a low-copy-number plasmid resulted in a strain that was able to both oxidize H2 and cause morbidity in mice within 11 days of inoculation; therefore, the avirulent phenotype of the triple mutant is not due to an unknown spurious mutation. We conclude that H2 utilization in a respiratory fashion is required for energy production to permit salmonella growth and subsequent virulence during infection.

Animals↗
PubMed2004

Response of very small (2 mm) porcine coronary arteries to balloon angioplasty and stent implantation.

OBJECTIVE: To investigate the response of very small coronary arteries to stent deployment and balloon angioplasty. SETTING: Normal porcine coronary arteries. METHODS: 24 pigs underwent intervention to two main coronary arteries, in segments 2.0 mm in diameter, with balloons whose diameter was 2.5 mm at standard pressure. Twelve arteries received a BiodivYsio small vessel (SV) stent; 12 an NIR SV stent; 12 standard BiodivYsio stent, and 12 balloon only. The arteries were harvested at 28 days, fixed, embedded in plastic, and cut and ground in cross section. The injury score and histomorphometry were assessed. RESULTS: The BiodivYsio SV stent was associated with 20% less injury (p = 0.16), a 30% larger lumen (p = 0.13), and a 25% smaller neointima (p = 0.03) than the NIR SV stent, despite identical oversize. The standard BiodivYsio stent exhibited less recoil but 29% greater injury (p = 0.01), 59% more neointima (p = 0.00), and 18% less lumen (p = 0.27) than the BiodivYsio SV. Of all interventions, balloon only was associated with little injury, little neointima, major vessel shrinkage, and the largest lumen. CONCLUSION: Despite uniform oversize dilatation, both injury and response varied widely in very small porcine coronary arteries, depending on whether a stent or balloon was used, the stent design, and the number and/or thickness of struts. The response to different stent designs is considerable and is related to the degree of injury.

Angioplasty, Balloon↗